Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function

Pei Wei; Chenjian Zhong; Xiaolan Yang; Futing Shu; Shichu Xiao; Teng Gong; Pengfei Luo; Li Li; Zhaohong Chen; Yongjun Zheng; Zhaofan Xia

doi:10.1093/burnst/tkaa020

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Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function

更新时间：2022-06-09

- Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function
- Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function
- Burns & Trauma 2020年8卷第1期
- 作者机构：
  
  1. Fujian Burn Institute
  2. Fujian Burn Medical Center
  3. Fujian Provincial Key Laboratory of Burn and Trauma
  4. Department of Burn Surgery
  5. Research Unit of key techniques for treatment of burns and combined burns and trauma injury
- 作者简介：
- 基金信息：
  
  This work was funded by the National Key R&D Program of China (2019YFA0110503), the National Nature Science Foundation of China (81701905, 81930057, 81772076, 81871559, 81571897), the Shanghai Pujiang Program (17PJD043), the Clinical Key Discipline Project of Shanghai and China;the Shanghai Health System Excellent Talent Training Program (2017BR037), the Fujian Burn Medical Center ([2017]171), the Key Clinical Specialty Discipline Construction Programme of Fujian, China ([2012]149) and the Fujian Provincial Key Laboratory of Burn and Trauma, China.
- DOI：10.1093/burnst/tkaa020
  中图分类号：
- 纸质出版日期：2020，
  
  网络出版日期：2020-9-7，
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Pei Wei, Chenjian Zhong, Xiaolan Yang, 等. Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function[J]. Burns & Trauma, 2020,8(1).

Pei Wei, Chenjian Zhong, Xiaolan Yang, Futing Shu, Shichu Xiao, Teng Gong, Pengfei Luo, Li Li, Zhaohong Chen, Yongjun Zheng, Zhaofan Xia, Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function, Burns & Trauma, Volume 8, 2020, tkaa020, https://doi.org/10.1093/burnst/tkaa020
Pei Wei, Chenjian Zhong, Xiaolan Yang, 等. Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function[J]. Burns & Trauma, 2020,8(1). DOI： 10.1093/burnst/tkaa020.

Pei Wei, Chenjian Zhong, Xiaolan Yang, Futing Shu, Shichu Xiao, Teng Gong, Pengfei Luo, Li Li, Zhaohong Chen, Yongjun Zheng, Zhaofan Xia, Exosomes derived from human amniotic epithelial cells accelerate diabetic wound healing via PI3K-AKT-mTOR-mediated promotion in angiogenesis and fibroblast function, Burns & Trauma, Volume 8, 2020, tkaa020, https://doi.org/10.1093/burnst/tkaa020 DOI：

摘要

Abstract

BackgroundDiabetic wounds are one of the most common and serious complications of diabetes mellitus

characterized by the dysfunction of wound-healing-related cells in quantity and quality. Our previous studies revealed that human amniotic epithelial cells (hAECs) could promote diabetic wound healing by paracrine action. Interestingly

numerous studies demonstrated that exosomes derived from stem cells are the critical paracrine vehicles for stem cell therapy. However

whether exosomes derived from hAECs (hAECs-Exos) mediate the effects of hAECs on diabetic wound healing remains unclear. This study aimed to investigate the biological effects of hAECs-Exos on diabetic wound healing and preliminarily elucidate the underlying mechanism.MethodshAECs-Exos were isolated by ultracentrifugation and identified by transmission electron microscopy

dynamic light scattering and flow cytometry. A series of in vitro functional analyses were performed to assess the regulatory effects of hAECs-Exos on human fibroblasts (HFBs) and human umbilical vein endothelial cells (HUVECs) in a high-glycemic microenvironment. High-throughput sequencing and bioinformatics analyses were conducted to speculate the related mechanisms of actions of hAECs-Exos on HFBs and HUVECs. Subsequently

the role of the candidate signaling pathway of hAECs-Exos in regulating the function of HUVECs and HFBs

as well as in diabetic wound healing

was assessed.ResultshAECs-Exos presented a cup- or sphere-shaped morphology with a mean diameter of 105.89 ± 10.36 nm

were positive for CD63 and TSG101 and could be internalized by HFBs and HUVECs. After that

hAECs-Exos not only significantly promoted the proliferation and migration of HFBs

but also facilitated the angiogenic activity of HUVECs in vitro. High-throughput sequencing revealed enriched miRNAs of hAECs-Exos involved in wound healing. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses have shown that the target genes of the top 15 miRNAs were highly enriched in the PI3K-AKT pathway. Further functional studies demonstrated that the PI3K-AKT-mTOR pathway was necessary for the induced biological effects of hAECs-Exos on HFBs and HUVECs

as well as on wound healing

in diabetic mice.ConclusionsOur findings demonstrated that hAECs-Exos represent a promising

novel strategy for diabetic wound healing by promoting angiogenesis and fibroblast function via activation of the PI3K-AKT-mTOR pathway.

关键词

Keywords

Human amniotic epithelial cellsExosomesDiabetic wound healingPI3K-AKT-mTOR

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